This invention belongs to the field of chemistry and relates to a formulation of saponins and chromans derivatives mixtures. The saponins are triterpenes types and chromans (TC) are hydrazones derivatives. This formulation is a therapeutic agent against tropical diseases for parenteral use and/or topical use.
Tropical medicine is the branch of medicine that deals with health problems that occur uniquely, are more widespread, or prove more difficult to control in tropical and subtropical regions. In practice, the term is often taken to refer to infectious diseases that thrive in hot, humid conditions, such as leishmaniasis, malaria, schistosomiasis, onchocerciasis, lymphatic filariasis, Chagas disease, African trypanosomiasis, and dengue.
Tropical diseases blight the lives of a billion people worldwide and threaten the health of millions more. An evaluation of their significance to public health and economies has convinced governments, donors, the pharmaceutical industry and other agencies, including nongovernmental organizations, to invest in preventing and controlling this diverse group of diseases.
Parasitic diseases caused by protozoan parasites such as Leishmania spp and Trypanosoma cruzi are affecting thousands of people around the world. Leishmaniasis is prevalent disease in 88 countries worldwide affecting 12 million people with 2.000.000 new cases per year, accounting for 500.000 cases of visceral leishmaniasis and 1.500.000 of cutaneous leishmaniasis. On the other hand, about 7.5 million people are infected with T. cruzi in 21 Latin-American countries, with approximately 41.000 new cases per year.
The massive displacement of populations, weather change, growing resistance to drugs treatment, lack of therapeutic alternatives and long treatments are creating a significant rise in these diseases, with the resulting increase in public health problems, mainly regarding poor people.
Solutions exist against the leishmaniasis like patents U.S. Pat. No. 8,287,921, EP 2337560, EP 2241317 A1, U.S. Pat. No. 6,872,713 and publication number US 2012/0207821 A1.
EP 2241317 A1 “Domperidone at a low daily dose for use in the treatment or prevention of a disease associated with an alteration of the immune response” (Ochoa, P., Homedes, J., Sabate, D.) 31 Mar. 2009 that relates to the use of domperidone or a pharmaceutically acceptable salt thereof at low doses to prevent and/or treat a disease associated with an alteration of the immune response such as Leishmaniasis.
Publication number US 2012/0207821 A1 “Liposomal formulation and use thereof” (Ali, N., Ghose, J., Bhowmick, S.) 10 May 2010 presents a liposomal formulation useful as a leishmanicidal agent, wherein said formulation comprising a single dose of therapeutically effective amount of an antileishmanial antimonial drug encapsulated in a cationic liposome consisting of a neutral lipid and a cationic lipid in a molar ratio of 7:2 respectively, wherein molar ratio of the neutral lipid and the cationic lipid to said drug is 7:2:0.2 to 0.25.
The U.S. Pat. No. 8,287,921 “Formulations against cutaneous leishmaniasis” (Rahman, Choudhary, Yousuf, Khan, Soomro, Perveen) 24 Jul. 2011 consisting essentially of a therapeutically effective amount of an ethyl acetate extract of aerial parts of Physalis minima dispersed in petroleum.
EP 2337560 A1 (WO2010017613A1) “Use of 5-hydroxy-2-hydroxymethyl-y-pyrone (hmp) as a leishmanicidal agent” (ALVES, CARVALHO, NASCIMENTO, Drumond, Silva, Oliveira) 14 Ago 2009 refers to the use of HMP (a secondary metabolite obtained from Aspergillus fungi) as an agent that intensifies the mechanism of macrophage activation, leading to the death of L. (Leishmania) amazonensis, the etiologic agent of cutaneous leishmaniasis.
Also Sapindus saponaria resin contain saponins type hederagenin and has been employed in traditional medicine as antihelmintic, and these types of compounds are reported like leishmanicide too.
The U.S. Pat. No. 6,872,713 “Antiprotozoal saponins” (Louis Jules Roger Marie Maes, Nils Albert Gilbert Germonprez, Luc Emiel Mathilde Van Puyvelde, Norbert G. M. De Kimpe, Tran Ngoc Ninh) 29 Mar. 2005 refers to saponins of formula (I), a stereoisomeric form thereof or a pharmaceutically acceptable addition salt thereof, wherein R1 to R12 have the meaning given in the description, can be isolated from plants of the family Myrsinaceae and used, to decrease the infectiousness of and reduce the mortality associated with protozoan parasites of the genus Leishmania which are responsible for a group of conditions known as leishmaniases, but the new patent of this application in a formulation of saponins and chromans derivatives mixture with better therapeutic results.
With regard to the extract of Sapindus saponaria, the application of patent US 2011/0274777 A1 “Method for extraction of material from a Sapindacea family fruit” (Jaime Toro Restrepo, James Alberto Jimenez Martinez, Luis Fernando Echeverri Lopez, Sandra Patricia Zapata Porras) 10 May 2010 provides a standardized method to obtain a material from Sapindacea family fruits, wherein the material provides a preparation of material used in combination with Swinglea glutinosa extract for the preparation enhances the ability of the Swinglea glutinosa extract to kill and prevent fungi, and to kill and repel insects and mites. In the present application of patent a new formulation is obtained mixed an extract from Sapindus saponaria in quantities from 20% until 60% with synthetic chroman for use as therapeutic agent against tropical diseases like leishmaniasis, american trypanosomiasis, malaria, african trypanosomiasis and fasciolosis.
On the other hands, some saponins form Maesa balansae showed high activity in vitro and in vivo assays against Leishmania, but the instant invention is a formulation of saponins and chromans derivatives mixture, where the saponins are triterpene types and chromans are hydrazones derivatives.